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LVVSC Oncologist Dr. Andrew Vaughan wrote this article on the diagnosis and treatment of canine mast cell tumors.

Canine Mast Cell Cancer
Mast cell cancer is the most common skin cancer in dogs. It is encountered most frequently in middle-aged to older dogs of many different breeds.The most commonly affected breeds are Pugs, Boxers, Bulldogs, and Boston Terriers but any breed can be affected. There may be an association between the development of mast cell cancer and prior chronic inflammation of the skin although this is unproven. Although sunlight exposure can contribute to other cancers of the skin in people and dogs, it has not been shown to cause mast cell cancer. Both male and female dogs can be affected and any area of the skin can be involved. Occasionally these tumors may arise within the oral cavity or within the abdominal organs (e.g. liver, spleen, gastrointestinal tract). The remaining discussion pertains primarily to tumors of the skin but similar principles may apply to tumors in other locations.

Clinical Signs
Most dogs are diagnosed with mast cell cancer as a result of the progressive growth of a tumor within or beneath their skin. These tumors can be under the skin and give rise to a fluctuant swelling that is not really visible but is discovered upon palpation by an owner, veterinarian, or groomer, or they may arise within the skin and produce a pinkish, raised, possibly ulcerated mass. Because of the inflammatory properties of mast cells, these tumors can wax-and-wane in size, be itchy or uncomfortable, cause substantial surrounding edema and swelling, and they may occasionally bleed or become ulcerated. Some mast cell tumors are seen to grow substantially in the days or weeks following recognition, other mast cell tumors may be present for many months or even years and not grow in any noticeable way. When mast cell cancers become large or if they spread to internal organs, they may cause systemic signs of illness. Such clinical signs may include stomach upset (vomiting, diarrhea or loss of appetite), lethargy, weakness, respiratory problems, or even acute collapse. Occasionally a patient can even die from the presence of advancing mast cell cancer. Fortunately with appropriate therapy this can often be avoided.

Diagnosis
Mast cell cancer can be diagnosed in numerous ways. Most frequently a needle aspirate or biopsy reveals numerous unusual mast cells in an affected area of skin. Thus, the diagnosis of mast cell cancer is usually not very challenging. Ultimately all skin growths should be evaluated by a veterinarian and aspirated or biopsied if they appear suspicious. Fortunately many skin growths in older dogs are not cancerous at all and only your veterinarian can tell the difference. If you have any questions or concerns about your pet’s skin, please point these out to our staff or your regular veterinarian so the problem can be thoroughly addressed. For patients with many skin growths we will often prepare a “body map” where all of the growths are documented, measured, and assessed to ensure that a record of the growths and their identity is maintained.

Biological Behavior
Mast cell cancers are described as being locally aggressive (meaning they readily invade normal skin and soft tissues in the area) and they also can spread to other places in the body (called metastasis). Because of this the disease may need to be treated with therapies that attempt to control the cancer both locally and systemically. The most common sites of metastasis for this cancer include the lymph nodes, liver, spleen, bone marrow, and possibly other sites within the body. For this reason your veterinarian may recommend that your pet undergo a lymph node aspirate, an abdominal ultrasound, chest radiographs (X-rays), a bone marrow aspirate, and/or other testing. These diagnostics help to determine how advanced the disease may be and what therapies may be most beneficial for your pet. Additionally, bloodwork and a urinalysis may be warranted to assess your pet’s systemic health.

One very important topic for understanding the biological behavior of mast cell tumors is grading. The grade of a tumor is determined by looking at a biopsy sample under the microscope and it can be used to predict the biologic behavior of a cancer. For mast cell tumors, grade has been found to be one of the most useful predictors of behavior. For example it has been shown that the metastatic rate for mast cell tumors varies dramatically with grade: grade I – <5%; grade II – 15-20%; grade III - >60%. Thus, a patient’s likelihood of cure with effective local therapy is heavily dependent on grade. In fact, most pets with surgically removed grade I or II mast cell tumors will not die from their cancer. The same is not true for grade III mast cell tumors, as the majority of patients will die from their disease, often within 4-6 months of surgery. Thus, for pets with grade III mast cell tumors, therapies in addition to surgery are highly recommended.

General Treatment Options – Deciding on an appropriate course of action
Not surprisingly, making decisions of how to proceed for a pet with cancer can be difficult. Owners and veterinarians alike must consider both the effectiveness of a form of therapy, the risks that a form of therapy may involve for the pet, and the practical aspects of treatment (hospital visits and costs of therapy). Thus, your veterinarian should discuss all of the options with you at great length prior to deciding how to proceed. If you have any questions that you feel have not been thoroughly addressed, please do not hesitate to ask one of our staff members.

Ultimately, the method in which mast cell tumors are treated depends on a number of factors:

i) the size, location and invasiveness of the local tumor,
ii) the presence or absence of metastatic disease,
iii) the grade of the tumor as determined via biopsy,
iv) the patient’s likely tolerance of the different forms of therapy (often determined by patient age and other on-going diseases), and
v) an owners interest in pursuing the different forms of therapy.

Fortunately for pets with small, low grade tumors that have not metastasized, surgery can often be curative. In other situations, however, surgery may not be likely to provide a cure. It is in these latter situations that other forms of therapy (radiation therapy and/or chemotherapy) may provide benefits and should be thoroughly considered.

Local Treatment Options – Surgery
It is critical to understand that mast cell cancers can be very invasive into the tissues surrounding the tumor. Thus, when trying to cure a mast cell tumor, a lot of normal appearing tissue surrounding the visible tumor may need to be removed. This is to ensure that any “fingers” or infiltrative extensions of cancer are removed along with the visible tumor (see diagram). This may require removal of as much as an inch of tissue in all directions around the visible mass to provide clean margins. Obviously such surgery is not always feasible or compassionate for patients with tumors in some areas of their bodies (e.g. face, near the anus or genitalia). When patients develop mast cell tumors on their limbs, we may consider amputation as a viable option for trying to cure the problem. In the absence of being able to provide wide margins, other forms of therapy may be considered (radiation therapy, chemotherapy).

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Local Treatment Options – Radiation therapy
In situations in which a mast cell tumor cannot be widely excised with surgery, we may recommend radiation therapy. While radiation therapy is usually not an effective treatment when used alone for mast cell tumors, it can be very effective when used in combination with surgery for tumors that can be partially, but not widely, excised (those with dirty margins in diagram above). This is due to the fact that radiation is very good for sterilizing (or killing) the microscopic extensions of malignant mast cells that surround a tumor. Thus, radiation therapy can often be a viable alternative to amputation for pets that have mast cell tumors on their limbs. Roughly 80% of dogs that have incompletely excised grade I or grade II mast cell tumors of the limbs will have long term (>3 year) cancer control with surgery and radiation therapy.

Unfortunately, radiation therapy does have substantial challenges:

i) Currently radiation therapy is not available for pets in Las Vegas. The closest treatment centers are in southern California and Phoenix
ii) Radiation therapy requires 19 daily treatments given over a month
iii) The side-effects of radiation can be substantial (irritation of the area being radiated) and may last from 2-4 weeks. This can be particularly problematic for areas like the face, toes, and anal regions.
iv) The cost of a course of radiation therapy is usually around $6000.

Obviously, our veterinarians will talk to you extensively about the pros and cons of this form of therapy before considering referral for radiation therapy.

Systemic Treatment of Mast Cell Tumors
Unfortunately some patients with mast cell cancer have a worse prognosis for which curative therapy may not be possible. Examples include patients with very large (inoperable) tumors, patients with a multitude of cutaneous mast cell tumors, patients with metastasis at the time of diagnosis regardless of grade, patients with tumors of the muzzle, genitalia or oral mucosa, or patients with grade III tumors. For each of these groups of patients, systemic medications are used to try to kill off mast cell cancer throughout the body. This can be a difficult task, and typically systemic cancer is controlled for a period of time, rather than cured. Thus, it is important to stress that many patients with more malignant mast cell tumors may still die of their disease in spite of surgery and/or systemic therapy. The goals of all forms of systemic therapy include prolongation of survival while maintaining a good quality of life. Examples of systemic therapies that can benefit patients with mast cell cancer include chemotherapy, steroid medications, pain medications, anti-histamines and antacids.

Systemic Treatment Options
Chemotherapy – General Concepts
Chemotherapy is a word that creates an instant emotional response in everyone. Chances are that you, or someone you know, has experienced chemotherapy for the treatment of cancer. The reality of chemotherapy for animals is generally different from that of human cancer patients. Most people are pleasantly surprised at how well their pets feel while undergoing chemotherapy. This is because the goals of veterinary oncology are to maintain quality of life both during and after chemotherapy. For this reason the doses of chemotherapy are typically lower than those used in human oncology. In this manner, chemotherapy can prolong lifespan for many patients with mast cell cancer without causing deterioration in quality of life. Unfortunately, at the doses typically administered to pets, it is rare that chemotherapy actually cures metastatic cancers. Rather chemotherapy is used to prolong lifespan for patients living with metastatic cancer while maintaining a good quality of life.

Chemotherapy – Possible Side-effects
Unfortunately chemotherapy can have a variable impact on a patient’s body. These drugs are toxic substances and some patients are more sensitive to them than others. This being said, about 80% of canine patients receiving chemotherapy have no notable side-effects. In the remaining 20% there can be gastrointestinal or immunosuppressive complications. In some instances (5%) these complications can be severe enough to warrant hospitalization for supportive care (e.g. intravenous fluids, antibiotics, anti-nausea drugs). Fortunately the majority of these problems resolve completely within a few days. In these instances future doses of chemotherapy are reduced to avoid such side-effects and maintain a good a quality of life. At anytime we are also free to stop giving chemotherapy. Unfortunately, in very rare instances patients can develop a severe bacterial infection called septicemia which can lead to death. Fortunately this is remarkably rare when appropriate monitoring and dosing are employed (<1% of patients). Other unique side-effects can arise from individual drugs and these are discussed in the other hand-outs we will provide for you. The most commonly used chemotherapy drugs for mast cell cancer include lomustine, vinblastine, chlorambucil and cyclophosphamide. Other novel drugs are now becoming available for dogs with mast cell cancer as discussed below. Chemotherapy – Outcome
The use of chemotherapy has advanced the treatment of canine mast cell cancer. The outcome of chemotherapy is very dependent on how advanced the mast cell cancer is within a pet’s body and this will be discussed with you in detail to ensure that you understand the potential benefits and risks prior to having your pet undergo such therapy.

Other medical management options
Palliative treatment options for mast cell cancer that can be of some benefit include steroidal anti-inflammatories (e.g. prednisone), anti-histamines (e.g. benadryl) and antacids (e.g. pepsid). These medications intend to control to complications of mast cell cancer by reducing inflammation within the tumor, throughout the body, or within the stomach. Unfortunately, for most pets, these approaches are of limited long-term benefit because they are unable to effectively kill the cancer cells themselves. It is also important to realize that if palliative therapy is pursued, it may make control of the cancer with more aggressive approaches (e.g. surgery, radiation, chemotherapy), more difficult at a later date.

The Future
In human oncology there are now numerous drugs that are termed “targeted chemotherapeutics”. These drugs have been designed to attack the specific molecular abnormalities within specific cancer cells that create the cancerous process in the first place. Drugs like gleevec (Imatinib) have revolutionized the treatment of human cancers like chronic myelogenous leukemia and gastrointestinal stromal tumors. Similarly, herceptin is now used for breast cancer and rituxan is used for some forms of lymphoma. One of our greatest challenges in veterinary medicine is finding analogs of these medications that will useful for treating canine and feline cancers. Thanks to recent work by a number of pharmaceutical companies, there are drugs now reaching the market that may start to revolutionize the management of canine mast cell cancer. Since these drugs are still undergoing extensive study, they are not readily available at this time, but we are hopeful that this will change.